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Research On Inhibit The NF-kappa B And MAPK Signaling Pathways Intervention Rabbit Atherosclerosis By Resveratrol

Posted on:2013-02-17Degree:MasterType:Thesis
Country:ChinaCandidate:W Q LiFull Text:PDF
GTID:2214330374455410Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
[Objective] To explore the effect of resveratrol on inflammation signal mechanism in atherosclerosis model rabbit.[Methods] Sixty-six males Japan white rabbit randomly divided into eight groups(9rabbits for group A to F,6rabbits for group G and H):group A(normal control)fed with normal feedstuff, group B,C(10weeks and20weeks model) fed with high cholesterol feedstuff, resveratrol intervention groupD,E,F,G(after fed20weeks high cholesterol feedstuff treat with resveratrol5mg/kg·d,15mg/kg·d,45mg/kg·d,80mg/kg·d), resveratrol prevent group H(treat with resveratrol80mg/kg·d as well as fed high cholesterol feedstuff). Except the model group B to be put to death after10weeks fed with high cholesterol, the rest are feeding32weeks to be put to death. The experimental animals were sacrificed32weekend and extraction of serum, separate out heart, aorta Specimens.Observation of the gross specimen; heart and aorta specimens, part of the dehydration is fixed, the production organization chip to HE dyed and determination caspase-3expression by immunohistochemical; The artery organization extraction tissue protein, used for protein immune imprinting western blotting test organization inflammation in signaling pathways MAPK (JNK, Erk, P38) and the NF-kappa B of the change.[Results]1, The group B executed, showing the formation of the subepicardial adipose tissue biopsy revealed early fatty streak and plaque formation, and successfully established atherosclerotic animal model. The group C serious fat tissue formation and large areas of fatty plaque formation.2, Resveratrol anti-atherosclerotic role of anatomy Facing view:Group A artery union without atherosclerotic plaque formation, C group had serious lipid plaque, fatpattern formation, in line with the lesions of atherosclerosis. Group D, E, F, group G artery atherosclerotic lesions was slightly reduced; the group D and E as effective as group F, G was significantly; group H than in normal group still lipid plaque formation, but lower than resveratrol in the intervention group (D, E, F, G group) has been reduced.3, Resveratrol anti-atherosclerotic mechanism of action-inhibition of inflammation of the key signaling pathway anti-artery atherosclerosis:Group B and C expression of inflammatory signaling pathway, NF-κB and MAPK (JNK, P38, Erk) phosphorylation than group A significantly activated (P<0.01); group C compared with group B, mild inflammatory changes (p<0.05); group D may be due to the dose low to inhibit the role of key signaling pathways of NF-κB and MAPK (Erk, P38) phosphorylation of (p>0.05); but weak inhibition of its phosphorylation in the MAPK-JNK pathway (p <0.05)ultra-high dose; group E and F by inhibiting NF-κB and MAPK (JNK, P38, of Erk) signaling pathway phosphorylation (p<0.05), reduce the arterial atherosclerotic inflammatory role; group G and H can inhibit NF-κB and MAPK (JNK, P38, of Erk) signaling pathway phosphorylation (p<0.01), significant improvement in the atherosclerotic inflammatory response4, Possible mechanisms of resveratrol artery atherosclerotic effect-anti-apoptosis: Group A, few caspase-3expression, caspase-3in group B and C significantly upregulated, group D, E, F and group G can reduce the expression of caspase-3(p <0.01, p<0.05, p<0.01, p<0.01), that is groupcertain anti-apoptotic effects, group G and H can significantly play anti-apoptotic role.[Conclusion] This study suggests that resveratrol have to reduce atherosclerotic plaque progression, anti-atherosclerotic role in the prevention of arterial atherosclerosis; possible mechanism of anti-inflammatory, anti-apoptotic. By inhibiting NF-κB and MAPK (JNK, P38, of Erk) phosphorylation of signaling pathways, play an anti-inflammatory effects, and the other by inhibiting the apoptotic factors caspase-3expression, played the anti-apoptotic effects, anti-inflammatory, anti-apoptotic effect was dose-effect relationship. Prevention group, suggesting that there is prevention of arterial atherosclerosis.
Keywords/Search Tags:Atherosclerosis, Resveratrol, Inflammation, MAPK pathways, NF-kappa B pathway
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